scholarly journals How Axon and Dendrite Branching Are Governed by Time, Energy, and Spatial Constraints

2021 ◽  
Author(s):  
Paheli Desai-Chowdhry ◽  
Alexander Brummer ◽  
Van Savage
Keyword(s):  
Time Delay ◽  
Branching Processes ◽  
Hemispheric Specialization ◽  
Cell Types ◽  
Conduction Time ◽  
Power Minimization ◽  
Spatial Constraints ◽  
Empirical Measures ◽  
Dendrite Branching ◽  
And Function

Neurons are connected by complex branching processes - axons and dendrites - that collectively process information for organisms to respond to their environment. Classifying neurons according to differences in structure or function is a fundamental part of neuroscience. Here, by constructing new biophysical theory and testing against our empirical measures of branching structure, we establish a correspondence between neuron structure and function as mediated by principles such as time or power minimization for information processing as well as spatial constraints for forming connections. Specifically, based on these principles, we use undetermined Lagrange multipliers to predict scaling ratios for axon and dendrite sizes across branching levels. We test our predictions for radius and length scale factors against those extracted from neuronal images, measured for cell types and species that range from insects to whales. Notably, our findings reveal that the branching of axons and peripheral nervous system neurons is mainly determined by time minimization, while dendritic branching is mainly determined by power minimization. Further comparison of different dendritic cell types reveals that Purkinje cell dendrite branching is constrained by material costs while motoneuron dendrite branching is constrained by conduction time delay over a range of species. Our model also predicts a quarter-power scaling relationship between conduction time delay and species body size, which is supported by experimental data and may help explain the emergence of hemispheric specialization in larger animals as a means to offset longer time delays.

Role of the 807 C/T Polymorphism of the α2 Gene in Platelet GP Ia Collagen Receptor Expression and Function

1999 ◽  
Vol 81 (06) ◽  
pp. 951-956 ◽  
Author(s):  
J. Corral ◽  
R. González-Conejero ◽  
J. Rivera ◽  
F. Ortuño ◽  
P. Aparicio ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Cell Types ◽  
Receptor Expression ◽  
Case Control Studies ◽  
Platelet Surface ◽  
Vitro Analysis ◽  
And Function ◽  
In Vitro Analysis

SummaryThe variability of the platelet GP Ia/IIa density has been associated with the 807 C/T polymorphism (Phe 224) of the GP Ia gene in American Caucasian population. We have investigated the genotype and allelic frequencies of this polymorphism in Spanish Caucasians. The T allele was found in 35% of the 284 blood donors analyzed. We confirmed in 159 healthy subjects a significant association between the 807 C/T polymorphism and the platelet GP Ia density. The T allele correlated with high number of GP Ia molecules on platelet surface. In addition, we observed a similar association of this polymorphism with the expression of this protein in other blood cell types. The platelet responsiveness to collagen was determined by “in vitro” analysis of the platelet activation and aggregation response. We found no significant differences in these functional platelet parameters according to the 807 C/T genotype. Finally, results from 3 case/control studies involving 302 consecutive patients (101 with coronary heart disease, 104 with cerebrovascular disease and 97 with deep venous thrombosis) determined that the 807 C/T polymorphism of the GP Ia gene does not represent a risk factor for arterial or venous thrombosis.

scholarly journals Epigenetic reprogramming of cell identity: lessons from development for regenerative medicine

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Amitava Basu ◽  
Vijay K. Tiwari
Keyword(s):  
Regenerative Medicine ◽  
Cell Types ◽  
Direct Conversion ◽  
Cellular Reprogramming ◽  
Specific Cell ◽  
Cell Type ◽  
Pathological Conditions ◽  
Gene Regulatory ◽  
Induced Pluripotent ◽  
And Function

AbstractEpigenetic mechanisms are known to define cell-type identity and function. Hence, reprogramming of one cell type into another essentially requires a rewiring of the underlying epigenome. Cellular reprogramming can convert somatic cells to induced pluripotent stem cells (iPSCs) that can be directed to differentiate to specific cell types. Trans-differentiation or direct reprogramming, on the other hand, involves the direct conversion of one cell type into another. In this review, we highlight how gene regulatory mechanisms identified to be critical for developmental processes were successfully used for cellular reprogramming of various cell types. We also discuss how the therapeutic use of the reprogrammed cells is beginning to revolutionize the field of regenerative medicine particularly in the repair and regeneration of damaged tissue and organs arising from pathological conditions or accidents. Lastly, we highlight some key challenges hindering the application of cellular reprogramming for therapeutic purposes.

scholarly journals Modelling the Human Placental Interface In Vitro—A Review

Micromachines ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 884
Author(s):  
Marta Cherubini ◽  
Scott Erickson ◽  
Kristina Haase
Keyword(s):  
Drug Testing ◽  
Cell Types ◽  
In Vitro Models ◽  
Placental Development ◽  
Scientific Challenge ◽  
Induced Pluripotent ◽  
And Function ◽  
And Control

Acting as the primary link between mother and fetus, the placenta is involved in regulating nutrient, oxygen, and waste exchange; thus, healthy placental development is crucial for a successful pregnancy. In line with the increasing demands of the fetus, the placenta evolves throughout pregnancy, making it a particularly difficult organ to study. Research into placental development and dysfunction poses a unique scientific challenge due to ethical constraints and the differences in morphology and function that exist between species. Recently, there have been increased efforts towards generating in vitro models of the human placenta. Advancements in the differentiation of human induced pluripotent stem cells (hiPSCs), microfluidics, and bioprinting have each contributed to the development of new models, which can be designed to closely match physiological in vivo conditions. By including relevant placental cell types and control over the microenvironment, these new in vitro models promise to reveal clues to the pathogenesis of placental dysfunction and facilitate drug testing across the maternal–fetal interface. In this minireview, we aim to highlight current in vitro placental models and their applications in the study of disease and discuss future avenues for these in vitro models.

scholarly journals Plasma membrane integrity in health and disease: significance and therapeutic potential

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Catarina Dias ◽  
Jesper Nylandsted
Keyword(s):  
Plasma Membrane ◽  
Therapeutic Potential ◽  
Calcium Influx ◽  
Membrane Integrity ◽  
Cell Types ◽  
Physical Parameters ◽  
Membrane Repair ◽  
Plasma Membrane Integrity ◽  
Repair Mechanisms ◽  
And Function

AbstractMaintenance of plasma membrane integrity is essential for normal cell viability and function. Thus, robust membrane repair mechanisms have evolved to counteract the eminent threat of a torn plasma membrane. Different repair mechanisms and the bio-physical parameters required for efficient repair are now emerging from different research groups. However, less is known about when these mechanisms come into play. This review focuses on the existence of membrane disruptions and repair mechanisms in both physiological and pathological conditions, and across multiple cell types, albeit to different degrees. Fundamentally, irrespective of the source of membrane disruption, aberrant calcium influx is the common stimulus that activates the membrane repair response. Inadequate repair responses can tip the balance between physiology and pathology, highlighting the significance of plasma membrane integrity. For example, an over-activated repair response can promote cancer invasion, while the inability to efficiently repair membrane can drive neurodegeneration and muscular dystrophies. The interdisciplinary view explored here emphasises the widespread potential of targeting plasma membrane repair mechanisms for therapeutic purposes.

scholarly journals Developmental enhancers and chromosome topology

Science ◽  
2018 ◽  
Vol 361 (6409) ◽  
pp. 1341-1345 ◽  
Author(s):  
Eileen E. M. Furlong ◽  
Michael Levine
Keyword(s):  
Three Dimensional ◽  
Cell Types ◽  
Living Cells ◽  
Specific Cell ◽  
Transcriptional Dynamics ◽  
Spatiotemporal Expression ◽  
Chromosome Topology ◽  
Classical Models ◽  
And Function ◽  
Target Promoters

Developmental enhancers mediate on/off patterns of gene expression in specific cell types at particular stages during metazoan embryogenesis. They typically integrate multiple signals and regulatory determinants to achieve precise spatiotemporal expression. Such enhancers can map quite far—one megabase or more—from the genes they regulate. How remote enhancers relay regulatory information to their target promoters is one of the central mysteries of genome organization and function. A variety of contrasting mechanisms have been proposed over the years, including enhancer tracking, linking, looping, and mobilization to transcription factories. We argue that extreme versions of these mechanisms cannot account for the transcriptional dynamics and precision seen in living cells, tissues, and embryos. We describe emerging evidence for dynamic three-dimensional hubs that combine different elements of the classical models.

scholarly journals Mapping calcium dynamics in a developing tubular structure

2020 ◽  
Author(s):  
Jorgen Hoyer ◽  
Morsal Saba ◽  
Daniel Dondorp ◽  
Kushal Kolar ◽  
Riccardo Esposito ◽  
...  
Keyword(s):  
Cell Types ◽  
Feedback Mechanism ◽  
Adult Brain ◽  
Actin Dynamics ◽  
Cytoskeletal Network ◽  
Notochord Cell ◽  
Wide Range ◽  
Store Operated Calcium Entry ◽  
And Function ◽  
Cell Intercalation

AbstractCalcium is a ubiquitous and versatile second messenger that plays a central role in the development and function of a wide range of cell types, tissues and organs. Despite significant recent progress in the understanding of calcium (Ca2+) signalling in organs such as the developing and adult brain, we have relatively little knowledge of the contribution of Ca2+ to the development of tubes, structures widely present in multicellular organisms. Here we image Ca2+ dynamics in the developing notochord of Ciona intestinalis. We show that notochord cells exhibit distinct Ca2+ dynamics during specific morphogenetic events such as cell intercalation, cell elongation and tubulogenesis. We used an optogenetically controlled Ca2+ actuator to show that sequestration of Ca2+ results in defective notochord cell intercalation, and pharmacological inhibition to reveal that stretch-activated ion channels (SACs), inositol triphosphate receptor (IP3R) signalling, Store Operated Calcium Entry (SOCE), Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) and gap junctions are required for regulating notochord Ca2+ activity during tubulogenesis. Cytoskeletal rearrangements drive the cell shape changes that accompany tubulogenesis. In line with this, we show that Ca2+ signalling modulates reorganization of the cytoskeletal network across the morphogenetic events leading up to and during tubulogenesis of the notochord. We additionally demonstrate that perturbation of the actin cytoskeleton drastically remodels Ca2+ dynamics, suggesting a feedback mechanism between actin dynamics and Ca2+ signalling during notochord development. This work provides a framework to quantitatively define how Ca2+ signalling regulates tubulogenesis using the notochord as model organ, a defining structure of all chordates.

scholarly journals Biogenesis of NDUFS3-less complex I indicates TMEM126A/OPA7 as an assembly factor of the ND4-module

2020 ◽  
Author(s):  
Luigi D’Angelo ◽  
Elisa Astro ◽  
Monica De Luise ◽  
Ivana Kurelac ◽  
Nikkitha Umesh-Ganesh ◽  
...  
Keyword(s):  
Mitochondrial Disease ◽  
Optic Atrophy ◽  
Complex I ◽  
Disease Gene ◽  
Mitochondrial Respiratory Chain ◽  
Cell Types ◽  
Catalytic Core ◽  
Assembly Factor ◽  
Functional Consequences ◽  
And Function

ABSTRACTComplex I (CI) is the largest enzyme of the mitochondrial respiratory chain and its defects are the main cause of mitochondrial disease. To understand the mechanisms regulating the extremely intricate biogenesis of this fundamental bioenergetic machine, we analyzed the structural and functional consequences of the ablation of NDUFS3, a non-catalytic core subunit. We prove that in diverse mammalian cell types a small amount of functional CI can still be detected in the complete absence of NDUFS3. In addition, we have determined the dynamics of CI disassembly when the amount of NDUFS3 is gradually decreased. The process of degradation of the complex occurs in a hierarchical and modular fashion where the ND4-module remains stable and bound to TMEM126A. We have thus, uncovered the function of TMEM126A, the product of a disease gene causing recessive optic atrophy, as a factor necessary for the correct assembly and function of CI.

scholarly journals The Skin Epilipidome in Stress, Aging, and Inflammation

2021 ◽  
Vol 11 ◽  
Author(s):  
Florian Gruber ◽  
Martina Marchetti-Deschmann ◽  
Christopher Kremslehner ◽  
Markus Schosserer
Keyword(s):  
Mass Spectrometry ◽  
Stress Responses ◽  
Immune Regulation ◽  
Biological Function ◽  
Cell Types ◽  
Skin Lipids ◽  
Surface Lipids ◽  
Mammalian Skin ◽  
Recent Developments ◽  
And Function

Lipids are highly diverse biomolecules crucial for the formation and function of cellular membranes, for metabolism, and for cellular signaling. In the mammalian skin, lipids additionally serve for the formation of the epidermal barrier and as surface lipids, together regulating permeability, physical properties, acidification and the antimicrobial defense. Recent advances in accuracy and specificity of mass spectrometry have allowed studying enzymatic and non-enzymatic modifications of lipids—the epilipidome—multiplying the known diversity of molecules in this class. As the skin is an organ that is frequently exposed to oxidative-, chemical- and thermal stress, and to injury and inflammation, it is an ideal organ to study epilipidome dynamics, their causes, and their biological consequences. Recent studies uncover loss or gain in biological function resulting from either specific modifications or the sum of the modifications of lipids. These studies suggest an important role for the epilipidome in stress responses and immune regulation in the skin. In this minireview we provide a short survey of the recent developments on causes and consequences of epilipidomic changes in the skin or in cell types that reside in the skin.

scholarly journals Profound functional and molecular diversity of mitochondria revealed by cell type-specific profiling in vivo

2018 ◽  
Author(s):  
Caroline Fecher ◽  
Laura Trovò ◽  
Stephan A. Müller ◽  
Nicolas Snaidero ◽  
Jennifer Wettmarshausen ◽  
...  
Keyword(s):  
Molecular Diversity ◽  
Molecular Level ◽  
Cell Types ◽  
Long Chain Fatty Acids ◽  
Cell Type ◽  
Mitochondrial Proteome ◽  
Novel Approach ◽  
Cell Type Specific ◽  
And Function

AbstractMitochondria vary in morphology and function in different tissues, however little is known about their molecular diversity among cell types. To investigate mitochondrial diversity in vivo, we developed an efficient protocol to isolate cell type-specific mitochondria based on a new MitoTag mouse. We profiled the mitochondrial proteome of three major neural cell types in cerebellum and identified a substantial number of differential mitochondrial markers for these cell types in mice and humans. Based on predictions from these proteomes, we demonstrate that astrocytic mitochondria metabolize long-chain fatty acids more efficiently than neurons. Moreover, we identified Rmdn3 as a major determinant of ER-mitochondria proximity in Purkinje cells. Our novel approach enables exploring mitochondrial diversity on the functional and molecular level in many in vivo contexts.

scholarly journals Spatial and single-cell transcriptional landscape of human cerebellar development

2020 ◽  
Author(s):  
Kimberly A. Aldinger ◽  
Zach Thomson ◽  
Parthiv Haldipur ◽  
Mei Deng ◽  
Andrew E. Timms ◽  
...  
Keyword(s):  
Single Cell ◽  
Emotional Regulation ◽  
Cell Types ◽  
Molecular Organization ◽  
Cerebellar Development ◽  
Disease Genes ◽  
Spatially Resolved ◽  
Human Cerebellum ◽  
Spatial Composition ◽  
And Function

ABSTRACTCerebellar development and function require precise regulation of molecular and cellular programs to coordinate motor functions and integrate network signals required for cognition and emotional regulation. However, molecular understanding of human cerebellar development is limited. Here, we combined spatially resolved and single-cell transcriptomics to systematically map the molecular, cellular, and spatial composition of early and mid-gestational human cerebellum. This enabled us to transcriptionally profile major cell types and examine the dynamics of gene expression within cell types and lineages across development. The resulting ‘Developmental Cell Atlas of the Human Cerebellum’ demonstrates that the molecular organization of the cerebellar anlage reflects cytoarchitecturally distinct regions and developmentally transient cell types that are insufficiently captured in bulk transcriptional profiles. By mapping disease genes onto cell types, we implicate the dysregulation of specific cerebellar cell types, especially Purkinje cells, in pediatric and adult neurological disorders. These data provide a critical resource for understanding human cerebellar development with implications for the cellular basis of cerebellar diseases.

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